Gap junctions are formed by a multigene family of membrane channel proteins, connexins (Cx). Connexins are divided into two subfamilies, ` and , based on amino acid sequence characteristics. The -type gap junction proteins 1 (Cx32) and 2 (Cx26) were originally described in mammalian liver. Six individual connexin molecules assemble into a hemi-channel spanning the plasma membrane. Two hexameric hemi-channels (connexons) emerge from adjacent cells into an extracellular gap between membrane domains (gap junctional plaques). The end-to-end interaction of connexons forms the active cell-to-cell channel. Multiple connexins can be expressed in the same tissue and the question is whether different connexins can assemble within or between hemi-channels. We are examining the structure of recombinant connexins. Mass measurements with the STEM on co-expressed connexins will let us see if 1Cx and 2Cx can co-assemble within the same hexamer or whether homomeric 1 and 2 connexons can form intracellular channels.